Efficacy and safety of surgery in renal carcinoma patients 75 years and older: a retrospective analysis.

OBJECTIVE: To investigate the efficacy and complications of surgical treatment in patients with renal cell carcinoma aged ≥ 75 years. METHODS: From January 2009 to May 2019, we assessed 166 patients aged 75 years and older, who either had radical nephrectomy (RN) or partial nephrectomy (PN) as treatments for diagnosed renal cell carcinoma. Patients were divided into one group of patients aged 75-79 years and the second group of patients ≥ 80 years. The complications and survival were compared between the two groups. RESULTS: All 166 patients were successfully operated on. Differences between the two groups were statistically significant in intraoperative and postoperative complications and Clavien-Dindo score of ≥ 1 (P = 0.02, P < 0.001, P = 0.001). Univariate analysis revealed no significant correlation between a Clavien-Dindo score ≥ 1 versus gender, body mass index (BMI), lack of symptoms, KPS, baseline GFR, postoperative GFR, tumor size, tumor location, surgical method, and transfusion or no transfusion (ALL P > 0.05). Multifactor analysis showed that age ≥ 80 years, partial nephrectomy, and operation time were independent predictors of a Clavien-Dindo score ≥ 1. No significant difference was found in OS between the two groups, (P < 0.0001), and no significant difference in CSS (P = 0.056). There was no significant difference in OS and CSS between the RN and PN groups (P = 0.143, P = 0.281, respectively). CONCLUSIONS: According to our findings, the overall safety of surgical therapy for elderly patients with renal cell carcinoma is adequate. PN should be carefully examined, especially over the age of 80. To select suitable patients based on an assessment of the tumor's complexity and patients' physical condition, such as age, underlying diseases and other conditions, technical feasibility, balance of benefits and a case-by-case.

Neutrophil extracellular traps in relationship to efficacy of systemic therapy for metastatic renal cell carcinoma.

BACKGROUND: The efficacy of systemic therapy regimens, such as immune checkpoint inhibitors and tyrosine kinase inhibitors (IO-TKI) and targeted therapy, for metastatic clear cell renal cell carcinoma (ccRCC) remains unpredictable due to the lack of effective biomarkers. Neutrophil extracellular trap (NET) plays an important role in promoting ccRCC. This study explores the NET predictive value of the efficacy in metastatic ccRCC. METHODS: In this retrospective study, patients with metastatic ccRCC who received targeted drugs and IO-TKI were included. Immunofluorescence staining was utilized to quantify the levels of tissue NETs through cell counts of H3Cit(+) and MPO(+) cells. RESULTS: A total of 183 patients with metastatic ccRCC were enrolled, including 150 patients who received TKIs and 33 patients who received IO-TKI. The levels of NETs in tumor tissue were significantly higher than in para-tumor tissue (p < 0.001). In terms of predicting drug efficacy, a correlation between NET levels and progression-free survival (PFS) was observed in the TKI with metachronous metastasis group (HR 1.73 [95% CI 1.02-2.91], log-rank p = 0.037), while no correlation was observed in the TKI with synchronous metastasis group and IO-TKI group. Regarding overall survival (OS), activated NET levels were associated with poor OS in both TKI (HR 1.60 [95% CI 1.05-2.43], log-rank p = 0.017) and IO-TKI group (HR 4.35 [95% CI 1.06-17.82], log-rank p =0.047). IMDC score (HR 1.462 [95% CI 1.030-2.075], p = 0.033) and tumor tissue NET levels (HR 1.733 [95% CI 1.165-2.579], p = 0.007) were independent prognostic risk factors for OS in patients with metastatic ccRCC.NET level was associated with poor OS in both TKI (HR 1.60 [95% CI 1.05-2.43], log-rank p = 0.017). CONCLUSIONS: The active NET levels in tumor tissue can predict drug efficacy in patients with metastatic ccRCC who received systemic therapy. Elevated levels of NETs in tumor tissue were also associated with poor efficacy in OS.

Chemotherapy combined with immunotherapy in primary female urethral squamous cell carcinoma: a case report.

Primary female urethral carcinomas are uncommon and have a low morbidity rate. Most of these patients have advanced illness with high invasion and a poor prognosis. There is no standard treatment, and multimodal therapy is recommended. The use of radiotherapy and chemotherapy were mostly reported in previous studies on advanced female urethral squamous cell carcinoma. We report that chemotherapy combined with a programmed death-1 (PD-1) inhibitor was effective in treating metastatic female urethral squamous cell carcinoma. During four cycles, we used systemic chemotherapy of albumin-paclitaxel + carboplatin in combination with a PD-1 inhibitor (toripalimab 240 mg) every 3 weeks, and a complete response was achieved. We performed a genetic test on the patient who had a tumor mutation burden of 5.7 mutations/Mb, tumor proportion score of 20%, and combined positive score of 20% (22C3). No recurrence or distant metastasis was found after 20 months of follow-up. In conclusion, in patients with positive PD-1 ligand 1 expression in primary female urethral squamous cell carcinoma, chemotherapy combined with PD-1 inhibitors may be effective. Larger sample studies are required to determine PD-1 ligand 1 expression and the curative effect of PD-1 inhibitors, as well as their effect on survival.

Improving the diagnosis of prostate cancer by telomerase-positive circulating tumor cells: A prospective pilot study.

BACKGROUND: Prostate-specific antigen (PSA) testing is limited in identifying prostate cancer (PCa) with modestly elevated PSA levels. Therefore, a robust method for the diagnosis of PCa is urgently needed. METHODS: A total of 203 men with a PSA level of ≥4 ng/ml were eligible for enrollment in this study from July 2018 to May 2021, and randomly divided into a training set (n=78) and a validation set (n=125). Circulating tumor cells (CTCs) were detected using telomerase-based CTC detection (TBCD), and the diagnostic ability was evaluated using receiver operating characteristic (ROC) and logistic regression analyses. FINDINGS: In the training set, the area under the curve (AUC) of CTCs was 0.842 with a sensitivity of 80.33% and specificity of 82.35%. In the validation set, the AUC of CTCs was 0.789, with a sensitivity of 79.31% and specificity of 81.58%. There was no significant difference between CTCs (AUC=0.793) and PSA (AUC=0.697) in the range of 4-50 ng/ml. In the ranges of 4-20 ng/ml and 4-10 ng/ml, the AUC of CTCs were 0.811 and 0.825, respectively, which were superior to the AUC of PSA (0.588 and 0.541). The sensitivity and specificity of CTCs in the three PSA groups were higher than 80%. Moreover, we further established a CTC+PSA combined model, which could significantly improve the diagnostic ability of a PSA level of '4-10 ng/ml'. INTERPRETATION: TBCD could be a valuable method for distinguishing PCa and benign prostatic disease, especially in the PSA diagnostic gray area of '4-10 ng/ml'.

Telomerase positive CTCs with PSMA high expression associated with prostate cancer metastasis.

Background: Whether circulating tumor cells (CTCs) with prostate-specific membrane antigen (PSMA) high expression was related to the metastatic progress in prostate cancer (PCa) remains explored. This study aimed to provide evidence to elucidate this relationship via the telomerase reverse transcriptase (TERT)-based CTC detection method. Methods: A total of 71 patients were enrolled and divided into the local PCa group (n=44) and metastatic PCa group (n=27). TERT-based CTC detection (TBCD) was used to detect CTCs. CTCs single-cell sequencing data were analyzed using gene ontology (GO) functional classification and enrichment. Results: The mean 'TERT+ CTCs' number was 6.11±9.63 in the metastatic group and 4.09±3.41 in the local group. GO enrichment analysis for 77 prostate CTCs single-cell sequencing confirmed that proliferation-related terms were enriched in the PSMA-high expression group, and 27 metastasis-related gene panels also had high expression in this group. Then, PSMA antibody was applied to mark the 'TERT+ CTCs'. The proportion of patients with 'TERT+ PSMA+ CTCs' was positively associated with the Gleason score. Furthermore, the proportion of 'TERT+ PSMA+ CTCs' patients was 48.15% in the metastatic group, significantly higher than 22.72% in the local group. Conclusions: This study suggested that TERT positive CTCs with high PSMA expression were associated with the PCa metastatic progress.

Neoadjuvant Chemotherapy-Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study.

PURPOSE: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. MATERIALS AND METHODS: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. RESULTS: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. CONCLUSION: After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Efficacy and Safety of Androgen-Deprivation Therapy Combined with Docetaxel Plus Prednisone in High-Burden Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of hormonal and synchronous docetaxel plus prednisone (DocP) in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: One hundred fifty-one cases with high-burden mHSPC diagnosed at 1 single center from January 2014 to August 2018 were analyzed retrospectively. Among them, 85 cases received androgen-deprivation therapy (ADT) within 3 months, along with 6 cycles of docetaxel + prednisone (treatment group), whereas 66 received ADT alone (control group). The primary end point was the median overall survival (OS), while the secondary outcomes included prostate-specific antigen (PSA) progression-free survival (PFS), radiographic PFS, and the proportion of PSA falling to 0.2 ng/mL. RESULTS: A total of 151 patients were included and followed up for a median of 34 months in this study. The median OS time in the treatment group was unavailable, but it was remarkably longer than that of the control group (P<0.001). In addition, the PFS of PSA in the treatment group and control group was 17.9 months and 9.2 months, respectively (P<0.001). Meanwhile, the radiographic PFS was 43 months in the treatment group and 19.8 months in the control group, respectively (P<0.001). The proportions of PSA falling to 0.2 ng/mL were 53.7% and 23.3%, respectively (P<0.001). However, there was no significant difference in the incidence of ≥3 toxic side effects between these 2 groups (P=0. 21). CONCLUSION: ADT combined with 6 cycles of docetaxel + prednisone chemotherapy benefits patients diagnosed with high-burden mHSPC in terms of the OS, PFS of PSA and radiographic, and the ratio of PSA falling to 0.2 ng/mL.